Effect of Doxycycline on Atherosclerosis: From Bench to Bedside

Rodríguez-Granillo, Gastón A.; Rodriguez-Granillo, Agustina; Milei, José

doi:10.2174/157489011794578419

Cited by 8 publications

(8 citation statements)

References 155 publications

(190 reference statements)

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“…Doxycycline is also beneficial in a mouse model of oculopharyngeal muscular dystrophy (37). Doxycycline and related molecules produce a large number of molecular and cellular changes in mammalian cells and tissues (18,(38)(39)(40)(41). In Lama2 2/2 skeletal muscle, doxycycline treatment may be beneficial by reducing inflammation and cell death (18).…”

Section: Discussionmentioning

confidence: 99%

Peripheral nerve pathology, including aberrant Schwann cell differentiation, is ameliorated by doxycycline in a laminin- 2-deficient mouse model of congenital muscular dystrophy

Homma

Beermann²,

Miller

2011

Human Molecular Genetics

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The most common form of childhood congenital muscular dystrophy, Type 1A (MDC1A), is caused by mutations in the human LAMA2 gene that encodes the laminin-α2 subunit. In addition to skeletal muscle deficits, MDC1A patients typically show a loss of peripheral nerve function. To identify the mechanisms underlying this loss of nerve function, we have examined pathology and cell differentiation in sciatic nerves and ventral roots of the laminin-α2-deficient (Lama2(-/-)) mice, which are models for MDC1A. We found that, compared with wild-type, sciatic nerves of Lama2(-/-) mice had a significant increase in both proliferating (Ki67+) cells and premyelinating (Oct6+) Schwann cells, but also had a significant decrease in both immature/non-myelinating [glial fibrillary acidic protein (GFAP)(+)] and myelinating (Krox20+) Schwann cells. To extend our previous work in which we found that doxycycline, which has multiple effects on mammalian cells, improves motor behavior and more than doubles the median life-span of Lama2(-/-) mice, we also determined how nerve pathology was affected by doxycycline treatment. We found that myelinating (Krox20+) Schwann cells were significantly increased in doxycycline-treated compared with untreated sciatic nerves. In addition, doxycycline-treated peripheral nerves had significantly less pathology as measured by assays such as amount of unmyelinated or disorganized axons. This study thus identified aberrant proliferation and differentiation of Schwann cells as key components of pathogenesis in peripheral nerves and provided proof-of-concept that pharmaceutical therapy can be of potential benefit for peripheral nerve dysfunction in MDC1A.

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Section: Discussionmentioning

confidence: 99%

Peripheral nerve pathology, including aberrant Schwann cell differentiation, is ameliorated by doxycycline in a laminin- 2-deficient mouse model of congenital muscular dystrophy

Homma

Beermann²,

Miller

2011

Human Molecular Genetics

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“…It was shown that doxycycline attenuates heart mechanical dysfunction and reduces inflammation in patients with coronary artery disease (CAD) [51]. In addition to its potential plaque stabilization in acute coronary syndromes properties, doxycycline shows promise in preventing ischemia-reperfusion injury and left ventricular remodeling [52]. Furthermore, clinical study demonstrated that doxycycline therapy led to downregulation of MMPs, dampening cardiac inflammation, and reduction of secondary myocardial infarction (MI) risk in coronary bypass patients [53].…”

Section: Biological Inhibitors Of Mmpsmentioning

confidence: 99%

Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability

Olejarz

Łacheta

Kubiak-Tomaszewska

2020

IJMS

146

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Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling and degradation of extracellular matrix (ECM) proteins. MMPs may modulate various cellular and signaling pathways in atherosclerosis responsible for progression and rupture of atherosclerotic plaques. The effect of MMPs polymorphisms and the expression of MMPs in both the atherosclerotic plaque and plasma was shown. They are independent predictors of atherosclerotic plaque instability in stable coronary heart disease (CHD) patients. Increased levels of MMPs in patients with advanced cardiovascular disease (CAD) and acute coronary syndrome (ACS) was associated with future risk of cardiovascular events. These data confirm that MMPs may be biomarkers in plaque instability as they target in potential drug therapies for atherosclerosis. They provide important prognostic information, independent of traditional risk factors, and may turn out to be useful in improving risk stratification.

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“…Percutaneous transluminal coronary angioplasty (PTCA) is the prominent treatment modality for severe CAD blockage, and drug eluting stents (DES) are often used to support the arterial wall, treat flow-limiting coronary stenosis, and reduce the risk of restenosis. However, DES or bare metal stents suffer from several limitations such as the presence of permanent metal within the artery, incomplete stent apposition, and late instent thrombosis and restenosis 2 . Drug eluting balloons (DEB) are an alternative to DES particularly in conditions where stent use might not be optimal, such as at vessel bifurcations and small tortuous vessels 3 .…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle eluting-angioplasty balloons to treat cardiovascular diseases

Iyer

Kuriakose

Yaman

et al. 2019

International Journal of Pharmaceutics

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Nanoparticles (NPs) can be used to locally deliver anti-restenosis drugs when they are infused directly to the injured arteries after intervention procedures such as angioplasty. However, the efficacy of transferring NPs via infusion to the arterial wall is limited, at least partially, due to poor NP retention on the inner artery wall. To improve NP retention, angioplasty balloons coated with drug-loaded NPs were fabricated via either layer-by-layer (LbL) electrostatic coating or acrylicbased hydrogel (AAH) coating techniques. Three types of NPs, namely poly (lactide-co-glycolide) (PLGA), biodegradable photo-luminescent PLGA and urethane doped polyester were studied. The transfer efficacy of NPs from various coatings to the arterial wall were further evaluated to find the optimal coating conditions. The ex vivo NP transfer studies showed significantly more NPs being transferred to the rat arterial wall after the angioplasty procedure by the AAH coating (95% transfer efficiency) compared to that of the LbL technique (60%) and dip coating (20%) under flow conditions (10 dyn/cm 2 ). Our results suggest that the AAH coating of drug-loaded NPs on the angioplasty balloon could potentially provide superior retention of drug-loaded NPs onto the arterial wall for a better local delivery of drug-loaded NPs to effectively treat arterial diseases.

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Effect of Doxycycline on Atherosclerosis: From Bench to Bedside

Cited by 8 publications

References 155 publications

Peripheral nerve pathology, including aberrant Schwann cell differentiation, is ameliorated by doxycycline in a laminin- 2-deficient mouse model of congenital muscular dystrophy

Peripheral nerve pathology, including aberrant Schwann cell differentiation, is ameliorated by doxycycline in a laminin- 2-deficient mouse model of congenital muscular dystrophy

Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability

Nanoparticle eluting-angioplasty balloons to treat cardiovascular diseases

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